1. Field of the Invention
This invention resides in the field of microfluidics, and in particular to certain features of an automated priming unit designed to fill the channels of a microfluidics device with liquids or gels. The invention is of particular interest to “lab-on-a-chip” systems for automated electrophoresis.
2. Description of the Prior Art
Electrophoresis is one example of a laboratory procedure that can be performed in an automated manner in a microfluidics device. Other examples are micro-scale binding assays and simulations of various processes and phenomena such as fluid dynamics, structural dynamics, thermal dynamics, and reaction kinetics. As a representative example, electrophoresis typifies the uses and advantages of microfluidics. The typical microfluidics device for electrophoresis is a small glass plate (or “chip”) affixed to a plastic carrier. The glass plate contains an array of microchannels in a network pattern that has been designed for optimum effect in electrophoresis. The various procedures involved in an electrophoretic analysis are performed by directing materials through the microchannels for purposes such as sample injection, separation, staining, and destaining. All of these procedures, plus detection and data analysis, are performed without user intervention. The components of the system as a whole, in addition to the chip and carrier, typically include an electrophoresis station which houses the electrical, optical, and hardware components needed to perform the electrophoresis, a priming station on which chips are loaded with appropriate liquids or gels and prepared for electrophoresis, a vortex station where samples and loading buffers are mixed inside the wells of the chip, software for system operation and data processing, and analysis kits for specific types of separations.
The typical microfluidics device for electrophoresis is a chip or block that contains an interconnected network of microchannels. One such device is shown in an exploded perspective view in FIG. 1 and in a side view in FIG. 2. The device 11 has a planar, layered body structure consisting of at least two layers, an upper layer 12 and a lower layer 13, bonded together. The upper surface 14 of the lower layer 13 is etched or otherwise cut or molded to contain a pattern of grooves 15. When the two layers are joined, these grooves form the microchannels within the chip that will contain the gel or other separation medium in which electrophoresis is to be performed. Apertures 16 in the upper layer provide expanded openings for access to the microchannels when the two layers are combined. FIG. 1 shows sixteen apertures in a 4×4 array. When such a device is used for electrophoresis, the separation medium, frequently in the form of a viscous liquid, is placed in one of the sixteen apertures, typically an aperture in one of the four corners of the array. The other apertures are often reserved for other liquids used in the electrophoretic procedure, such as buffers, staining solutions, and samples.
In use, the microfluidics device 11 of FIGS. 1 and 2 is enclosed in a carrier 21, commonly termed a “caddy.” A typical such carrier is shown in FIG. 3. The carrier fully encases the microfluidics device and thereby removes the device from visibility in this view. The shape of the carrier can vary and will be selected to coordinate its use with the remaining units and components with which the microfluidics device is used. The caddy shown in FIG. 3 is generally rectangular with two curved opposing edges 22, 23. The carrier contains an array of cylindrical extensions 24 with the same spacing and arrangement as the apertures 16 (FIG. 1) of the microfluidics device and these extensions are aligned with the apertures when the microfluidics device is inserted in the carrier. These extensions serve as reservoirs over the apertures to hold the gel or liquid that will pass through the apertures into the microchannels when pressure is applied. Although not shown, the carrier 21 also contains various structural and connecting features that permit electrophoresis (or other procedures) to be performed on the fluids that will be placed in the microchannels without removing the microfluidics device from the carrier.
One factor that affects the reliability, reproducibility, and ease of use of a microfluidics device is the manner in which the microchannels are primed with the gel or any of the liquids needed for the electrophoretic analysis. It is known, for example, that dyes in separation matrices tend to bind to the walls of the microchannels during priming. Wall-bound dye in the detection channel becomes background signal that adversely affects the detection sensitivity of the instrument and causes nonuniformity between different chips. Chips intended for use with matrices containing RNA, for example, are particularly susceptible to dye binding due to the cationic nature of the RNA dye. In general, differences in the amounts of dye bound to the walls can be minimized or eliminated by controlling the time during which the walls are exposed to dye. In chips used for protein analyses, for example, a common practice is to limit the priming time to a maximum of one minute. In chips used for analyses of other species, such as nucleic acids, a shorter maximum priming time may be required. The present invention offers several features that facilitate the priming process and provide improved control over the exposure time as well as the amounts of gel or liquid that are placed in the microchannels.